Scimex: Craving that after-work burger with fries? Melbourne scientists have uncovered the exact reasons behind salt’s addictive nature. Dr Craig Smith from the Florey Institute of Neuroscience and Mental 
Health and Deakin University’s School of Medicine, has shown how a 
specific circuit in the brain’s opioid system is responsible for making 
us seek out salt. The discovery points the way toward drug treatments 
that could reduce our intake of high salt foods.
Australians eat too much salt and we are putting ourselves at risk of
 high blood pressure which accounts for about half of all strokes, heart
 disease and chronic kidney disease deaths. Almost one in 20 deaths in 
Victoria is attributable to high salt intake – six times the annual road
 toll.
“Modern western diets high in salt also tend to be high in things 
like fat and sugar – which have also been shown to possess addictive 
properties. Put these three ingredients together and you have an almost 
irresistible recipe for obesity,” says Dr Smith.
“Our bodies have multiple forms of ‘natural opioids’ – those 
molecules released after you enjoy a particularly energetic session of 
exercise (or love-making), drinking water when thirsty or eating salt 
after sweating. Interestingly, these same molecules also control our 
craving of these rewards. Although scientists know that the opioid 
system regulates salt seeking, the exact circuit has, until now, 
remained a mystery.
Using mice that had salt removed from their diet, Dr Smith and the 
team used three separate opioid blockers to work out which specific 
circuit was activated when the mice drank salty water. “Two blockers did
 nothing. But a third, naloxonazine, drastically reduced the amount of 
salt consumed by the animals,” he says.
As well as discovering the exact opioid receptor system involved in 
salt reward, the team has built upon four years of work to identify the 
part of the brain where it happens. Although opioid receptors are found 
throughout the brain, giving salt-depleted mice access to salty water 
activated receptors in a specific brain area called the central amygdala
 – where emotions are processed. This allowed the researchers to block 
opioids only in that particular brain region, and the salt-depleted mice
 were no longer interested in drinking salty water.
According to Dr Smith: “Natural opioids, like endorphins, bind to 
specific receptors in the brain. These findings open the way for us to 
study this salt seeking circuit in humans using magnetic resonance 
imaging and other techniques, to then develop targeted drugs to inhibit 
salt craving and promote more healthy dietary choices. If processed food
 producers are slow to respond to the need to reduce salt in their 
products, this could be another way to lower deaths associated with high
 salt intake.”
The latest findings could also lead to improved treatments for other 
forms of addiction. Addiction to opiates like heroin is a phenomenon of 
the last 5000 years. This research suggests opiates have “highjacked” 
the ancient genetic organization of salt appetite, which evolved over 
300 million years. 
Opiates activate the same receptors in our brain that are stimulated 
by salt – only much more strongly than even the most delicious burger 
and fries. Just as future treatments might reduce salt craving, they 
might also reduce an addict’s craving for heroin.
The research was funded with a National Health and Medical Research Council project grant, and published in the Early Edition of the current issue of Proceedings of the National Academy of Science.